Pathologic analyses of non-overt necrotizing type Kikuchi and Fujimoto's disease

Twenty-eight cases of non-overt necrotizing type Kikuchi-Fujimoto disease (KF disease, histiocytic necrotizing lymphadenitis) were investigated clinicopathologically, immunohistochemically and electron microscopically in order to analyze the nature of this disease. In addition, investigations to detect the presence of Epstein-Barr virus (EBV) using the polymerase chain reaction (PCR) and in situ hybridization (ISH) were also performed as a high incidence of positive serum immunoreactivity to EBV had been revealed in the cases examined. The clinical features were an equal male to female ratio, mean age of 26 years, mild leukopenia and about 40% association with fever over 38 degrees C. The major particular pathologic features were: (i) varying amounts of nuclear debris in the pathologic areas, identified as apoptosis by electron microscopy; (ii) presence of medium to large sized transformed lymphocytes (immunoblasts), a very small number of them positive for both UCHL1 and L26, and plasmacytoid cells, some of them positive for UCHL1; and (iii) characteristically shaped histiocytes predominant in the pathologic areas, with irregular nuclei and strongly positive for anti-lysozyme and anti-alpha 1-antitrypsin antibodies. Investigations with PCR and ISH revealed a complete absence of EBV in these cases despite excellent results for positive controls. It was therefore considered that EBV was not a causative virus for KF disease.